We plan to continue to develop and assess the efficacy of novel approaches for the treatment of malignant disease based on studies in dogs with spontaneously occurring malignancies. Studies in dogs with malignant lymphoma have shown that some dogs treated with chemotherapy, total body irradiation (TBI) and autologous marrow infusion can be cured of their disease but that most will ultimately develop recurrent lymphoma. We propose to determine whether recurrent lymphoma results from infusion of malignant cells in the autologous marrow or from failure of TBI to eradicate all malignant cells. We will investigate the mechanism of cure in dogs free of disease after therapy by determining whether such dogs are immune to autologous lymphoma cells. We also plan to study the graft-versus-tumor effect of allogeneic marrow transplantation using a new immunosuppressive agent, cyclosporin A. In dogs with osteogenic sarcoma, we wish to test the hypothesis that growth of metastatic tumor can be inhibited by interference with hemostatic mechanisms. We also plan to assess whether the results of in vitro assays of cell-mediated and humoral immunity performed serially before and after amputation in dogs not given adjuvant chemotherapy correlate with in vivo events. We also will compare the effectiveness of conventional versus high dose methotrexate as cytoreductive chemotherapy administered before amputation. We also plan to study the feasibility and effectiveness of positron emission tomography in tumor imaging.